Anna Norrby-Teglund group

Our overall goal is to decipher mechanisms contributing to severe manifestations of acute bacterial infections and thereby identify targets for therapeutic intervention. The research is translational in nature and is based largely on clinical isolates, patient materials and human cell and tissue model systems that mimic the clinical setting.

Of particular interest are the two Gram-positive bacteria Streptococcus pyogenes and Staphylococcus aureus, both of which may cause highly aggressive invasive infections such as toxic shock, necrotizing pneumonia and necrotizing fasciitis that are associated with substantial morbidity and mortality. The research strives to decipher bacterial properties contributing to disease outcome and events underlying tissue injury. A specific theme is to evaluate immunotherapeutic strategies in these diseases.

Members

BSc in biology (microbiology) at Umeå University (1989), PhD in clinical bacteriology at Umeå University (1994), postdoctoral studies at Univ. of Tennessee, Memphis, US (1994-97), Associate Professor at KI (1999). Establishment of research group at Karolinska Institutet (KI)(1997). Professor in medical microbial pathogenesis at KI (2008).

Projects

Novel mediators/markers of sepsis

Recent studies have shown that the systemic inflammatory response involved in the pathophysiology of sepsis is more prolonged and heterogeneous in nature than previously thought, including also newly discovered mediators. Our research aims to decipher the mechanistic action of these mediators, in particular the neutrophil-derived mediators resistin and heparin-binding protein (HBP), which we have shown to be significantly associated with severity of infection (Crit Care Med, 2007; J Immunol. 2009; Cell 2004).

Another inflammatory mediator was found to have prognostic value when used in combination with APACHE II score. A novel prediction rule with four levels of risk in sepsis based on APACHE II score and serum suPAR was proposed (Giamarellos et al Crit Care 2012).

Collaborations

Herwald, Åkesson,

Linder: Lund University.

Immunomodulatory properties of S. pyogenes

S. pyogenes primarily cause severe infections by modulating and exploiting immune cells. This project focuses on the interaction between streptococci and phagocytic cells, in particular immune escape events. We identified intracellular persistence as a significant pathogenic mechanism contributing to bacterial eradication failure at the tissue site of infection (PLoS Med 2006). Further studies by Hertzén et al (J innate Immun. 2010) provided evidence that intracellular survival is linked to impaired phagolysosomal maturation. A differential gene expression is evident during the early compared to late stages of the bacterial intracellular cycle (PLoS One, 2012).

Collaborations

Holden

Imperial College, UK

Kotb, Univ Cincinatti, US

Nizet, Univ. California, San Diego, US

Both beneficial and detrimental effects of neutrophil responses have been emphasized in severe streptococcal infections. Our patient biopsy data (Infect Immun 2008, J Immunol. 2009) are in line with the detrimental effect of neutrophils, as neutrophil infiltration and degree of granule proteins correlate with bacterial load and severity of tissue disease. These findings will be further explored in primary human cell cultures and 3D-organotypic skin and lung tissue models.

Collaboration

Mattias Svensson, KI.

S. aureus: pathogenesis and identification of novel targets for intervention

Severe invasive S. aureus represent a significant health problem globally with certain clones giving rise to unusually severe pathological signs, such as necrotizing pneumonia and fasciitis. Several different putative virulence determinants have been described including the greatly debated PVL. A recent study by Löffler et al (PLoS Path 2010) showed striking differences in host susceptibility to PVL with human cells being highly susceptible. Here we aim to decipher the role of specific toxins and their potential synergistic effects in the pathogenesis of these infections, by use of human cell and 3D organotypic tissue cultures and well-characterized clinical isolates.

Collaborations

Mattias Svensson, KI

Arakere, Bangalore, India

Etienne, Lyon Univ, France

Necrotizing soft tissue infections: EU-project INFECT

In January 2013, the EU-funded project INFECT (www.fp7infect.eu) was launched and will be ongoing for five years. INFECT involves 14 partners in Sweden, Europe and the US. The project was initiated by Norrby-Teglund, who is also the coordinator of INFECT.

The focus of the project is to advance the understanding of necrotizing soft tissue infections (NSTI) that are associated with high mortality rates (>30%) and often require extensive surgery of the tissue, sometimes even amputation of the affected body parts. INFECT aims to identify risk factors and disease mechanisms that contribute to tissue damage and fatal processes. This is the first time an integrated systems biology approach is used in necrotizing deep tissue infections using patient samples and clinically relevant experimental models.

Open positions

If you are interested in doing research in our group, as a degree project, PhD student or postdoc, please feel free to contact the group leader Anna Norrby-Teglund. We are always interested in discussing with talented potential co-workers.